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Published on: November 12, 2015
Allergic disease and keratoconus: A two-sample univariable and multivariable Mendelian randomization study
Hanlu Xu1,2, Yajing Wen1,2, Huikang Zheng1,2
1National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, China.
Background:
There is accumulating evidence that allergy is a risk factor for keratoconus. Nonetheless the association between allergic disease and keratoconus remains controversial. We performed a two-sample Mendelian randomization (MR) study to determine the putative causal association of 4 allergic diseases (allergic conjunctivitis, allergic asthma, allergic rhinitis and atopic dermatitis) with keratoconus.
Methods:
Summary statistics were obtained from genome-wide association studies (GWAS) of allergic conjunctivitis (AC) (20,958 cases and 356,319 controls), allergic asthma (AA) (9631 cases and 210,122 controls), allergic rhinitis (AR) (11,009 cases and 359,149 controls), atopic dermatitis (AD) (13,473 cases and 336,589 controls), keratoconus (KC) (2116 cases and 24,626 controls) and 91 circulating inflammatory cytokines (n = 14,824). Two-sample univariable and multivariable MR analyses were performed. A two-step MR was then applied to determine whether systemic inflammatory cytokines mediated the effect of allergic disease on keratoconus.
Results:
The causal odds ratio (OR) estimate of genetically determined KC was 1.66 (95% CI: 1.32-2.08; P < 0.001) for AC, 1.29 (95% CI: 1.10-1.51, P = 0.0014) for AA, 1.39 (95% CI: 1.15-1.68; P < 0.001) for AR and 1.30 (95% CI: 1.17-1.45, P < 0.001) for AD. Multivariable MR indicated a suggestive association between AC and KC after conditioning on other allergic diseases (OR 1.61; 95% CI: 1.10-2.34; P adjusted = 0.054). Two-step MR revealed that the effect was not mediated by systemic inflammatory cytokines.
Conclusions:
Our findings provide evidence of a potential causal relationship between AC and KC. The effect of AC on KC may be mediated via other systemic inflammatory cytokines not included in the present study, or by alternative mechanisms. These findings may offer insight for prevention and intervention strategies to lower the risk of KC in patients with AC.
Insights
Allergic conjunctivitis (AC) is a potential causal risk factor for keratoconus (KC). This study found a causal link between AC and KC, suggesting new prevention strategies for patients with allergies.
Area of Science:
- Ophthalmology
- Genetics
- Immunology
Background:
- Accumulating evidence suggests allergies may increase keratoconus (KC) risk, but this association remains debated.
- A two-sample Mendelian randomization (MR) study investigated the causal link between four allergic diseases and KC.
Purpose of the Study:
- To determine the putative causal association between allergic conjunctivitis (AC), allergic asthma (AA), allergic rhinitis (AR), and atopic dermatitis (AD) with keratoconus (KC).
- To explore potential mediation by systemic inflammatory cytokines in the AC-KC relationship.
Main Methods:
- Utilized genome-wide association study (GWAS) summary statistics for allergic diseases and KC.
- Performed univariable, multivariable, and two-step MR analyses, including analysis of 91 circulating inflammatory cytokines.
Main Results:
- Genetically determined KC showed significant causal odds ratios for AC (1.66), AA (1.29), AR (1.39), and AD (1.30).
- Allergic conjunctivitis (AC) remained suggestively associated with KC after adjusting for other allergic diseases (OR 1.61).
- Two-step MR indicated no mediation by the studied systemic inflammatory cytokines.
Conclusions:
- Findings provide evidence for a potential causal relationship between allergic conjunctivitis (AC) and keratoconus (KC).
- The AC-KC pathway may involve unmeasured inflammatory cytokines or alternative mechanisms.
- Results may inform prevention and intervention strategies for reducing KC risk in AC patients.
